Adding a Live Biotherapeutic Product (CBM588) to Pembrolizumab for the Treatment of Renal Cell Cancer After Surgery

NCT07037004 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24709NCI-2025-04100P30CA033572
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial compares the effect of adding a Live Biotherapeutic Product called CBM588 to pembrolizumab versus pembrolizumab alone in preventing return of disease (recurrence) after surgery for patients with renal cell cancer. Pembrolizumab is an immune checkpoint inhibitor. Immunotherapy with monoclonal antibodies such as pembrolizumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab is approved for the treatment of renal cell cancer after surgery. Research has shown that changes to the composition of the healthy bacteria in the body (the microbiome), may improve a patient's response to treatment with immunotherapy. CBM588, a Live Biotherapeutic Product (LBP) containing a bacteria called Clostridium butyricum, has been shown to improve outcomes in patients treated with immunotherapy for other types of cancer. Adding CBM588 to treatment with pembrolizumab after surgery may cause changes in the microbiome that improve patient response to treatment and reduce disease recurrence, compared to pembrolizumab alone.

Conditions

Clear Cell Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage II Renal Cell Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Change in interleukin (IL)-12 levels

  A two-sample t-test will be used to test the difference in the changes in IL-12 production for the two treatment arms. A Wilcoxon rank-sum test will be used if the changes are not normally distributed (p\< 0.05 by a Shapiro-Wilks test).

  Baseline to week 12

Secondary Outcomes (7)

• Recurrence-free survival (RFS)

  From randomization to disease recurrence or death, assessed up to 1 year

• Overall survival (OS)

  From randomization to death from any cause, assessed up to 1 year

• Shannon diversity index

  Baseline to week 12

• Proportion of circulating regulatory T cells (Tregs)

  Baseline to week 12

• Proportion of circulating myeloid derived suppressor cells (MDSCs)

  Baseline to week 12

Study Arms (2)

Arm 1 (CBM588, pembrolizumab)

EXPERIMENTAL

Patients receive CBM588 PO BID on days 1-21 or days 1-42 of each cycle and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.

Procedure: Biospecimen Collection; Drug: Clostridium butyricum CBM588 Strain; Procedure: Computed Tomography; Biological: Pembrolizumab

Arm 2 (pembrolizumab)

ACTIVE COMPARATOR

Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Pembrolizumab

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (CBM588, pembrolizumab); Arm 2 (pembrolizumab)

Clostridium butyricum CBM588 Strain DRUG

Given PO

Also known as: C. butyricum CBM588 Strain, C. butyricum MIYAIRI Strain, C. butyricum Strain MIYAIRI 588, CBM588, Clostridium butyricum MIYAIRI 588, Clostridium butyricum MIYAIRI 588 Strain, MIYAIRI 588, MIYAIRI 588 Strain of C. butyricum

Arm 1 (CBM588, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm 1 (CBM588, pembrolizumab); Arm 2 (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Arm 1 (CBM588, pembrolizumab); Arm 2 (pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide informed consent for the trial
• Histological confirmation of renal cell carcinoma (RCC) with a clear-cell or sarcomatoid component
• Pathologic stage of pT2, G4 or sarcomatoid, N0M0; pT3, any grade, N0M0; pT4, any grade, N0M0; pTany, any grade, N+M0; or M1 no evidence of disease (NED) after resection
• No prior systemic immunotherapy for RCC
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Males and females, ages ≥ 18
• Any ethnicity or race
• Calculated creatinine clearance ≥ 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if liver metastases are present)
• Total bilirubin \< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin up to 3.0 mg/dL)
• Adequate bone marrow function defined by any of the following laboratory test findings: white blood cells (WBC) \> 2,000/mm\^3, neutrophils \> 1,500/mm\^3, platelets \> 100,000/mm\^3
• Female subjects of child-bearing potential and female partners of male subjects must agree to use a highly effective method of contraception during treatment and for at least 5 months after the last dose
• Highly effective methods of contraception include: tubal ligation, an approved hormonal contraceptive such as oral contraceptives, patches, implants, injections, rings or hormonally impregnated intrauterine device (IUD), or IUD

You may not qualify if:

• Prior radiation or anti-PD1, anti-PDL1, or anti-CTLA-4 therapy for RCC
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Baseline pulse oximetry less than 92% "on room air"
• Current use, or intent to use probiotics, prebiotics, yogurt, bacterial fortified foods and other natural supplements ≤ 2 weeks prior to treatment initiation and during the period of treatment
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Not recovered to ≤ grade 1 toxicities related to any prior therapy before administration of study drug
• Women who are pregnant or breastfeeding
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Specimen Handling; pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Wesley Yip

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2025
• First Posted: June 25, 2025
• Study Start: May 4, 2026
• Primary Completion (Estimated): October 24, 2028
• Study Completion (Estimated): October 24, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (2)